Lopinavir/r containing regimen superior to nevirapine containing regimen in women previously exposed to single dose nevirapine

Shahin Lockman presented findings from the A5208 (OCTANE) study on behalf of the study team. [1]

OCTANE is a comparison of treatment regimens in women previously exposed to single dose nevirapine (NVP). We reported early results from this study previously in the November/December 2008 issue of HTB, following the DSMB recommendation that OCTANE Trial 1 be unblinded and interim findings made public, due to superior results in the lopinavir/r (LPV/r) vs the nevirapine (NVP) containing arm of the study. [2]

Dr Lockman showed further data from Trial 1, in which 241 women were randomised to receive either NVP+tenofovir (TDF)+ emtricitabine (FTC) (n=121)or LPV/r+TDF+FTC (n=120).

Results were from an intent-to-treat analysis. 41 women reached a primary endpoint of virologic failure (defined as <1 log10 below baseline, 12 weeks after starting treatment or as viral load >/=400 copies/mL at or after 24 weeks of treatment) or death. Of these 31 (26%) were in the NVP and 10 (8%) in the LPV/r arm, HR 3.55(95% CI 1.71,7.34), p=0.0007.

Virologic failure occurred in 22% of women in the NVP arm and 8% in the LPV/r arm, p=0.002. And 3% vs 1% died in the NVP and LPV/r arms respectively, p=0.21. These deaths were not associated with antiretroviral treatment.

44 women discontinued NVP or LPV/r in their first regimen, of these 38(31%) were in the NVP and 6 (5%) in the LPV/r arms respectively, HR, 7.43 (95% CI 3.14, 17.59), p=0.0001.

Of 239/241 women for whom baseline resistance test results were available 33 (14%) had NVP associated mutations (28, K103N and 5, Y181C). The median time since single dose NVP exposure was 11 months in this group of women vs 17 months in 206 women without NVP resistance, p=0.024.

An analysis of proportions of women with virologic failure or death by presence of baseline NVP resistance, revealed an overall rate of 25% in the NVP arm (n=120) vs 8% in the LPV/r arm (n=119), p=0.001. 73% in the NVP arm vs 6% in the LPV/r arm had resistance, p=006. 18% in the NVP arm and 9% in the LPV/r arm had no NVP resistance, p=0.057. (Interaction of difference between treatment arms and presence or absence of resistance, p=0.04).

And proportions of women with virologic failure or death by time since last single dose NVP exposure were: 37% in the NVP arm vs 3% in the LPV/r arm in women receiving treatment after a 6 to <12 month interval since single dose NVP exposure, p=0.008 (n=78); 26% vs 12% in women with a 12 to <24 month interval, p=0.56 (n=98); and 12% vs 10% in women with >/= 24 month interval, p=0.72 (n=65). (Interaction of difference between treatment arms and continuous time since last single dose NVP exposure, p=0.2).

She noted that these findings might not apply to women receiving other PMTCT interventions with single dose NVP such as short course AZT or with AZT/3TC tail. Also that treatment success in the LPV/r was very high. The OCTANE investigators are waiting on results from Trial 2 (LPV/r vs NVP containing HAART in NVP unexposed women) in order to fully interpret Trial 1 results.

Lopinavir/r containing regimen superior to nevirapine containing regimen in women previously exposed to single dose nevirapine

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